The role of single cardiac fibers in the origin of cardiac arrhythmias will be studied. The arrhythmias of special interest are those which arise during ischemia or infarction of the ventricles. The transmembrane potentials of Purkinje and ventricular muscle cells contained in tissue preparations isolated from dog hearts will be recorded using glass microelectrodes. The specific aims are to study the factors involved in producing a distinct type of membrane action potential termed a slow response. The characteristics and behavior of cells which develop the slow response type of action potential also will be studied. Slow responses are an abnormal type of action potential in Purkinje and ventricular cells which alter the properties of impulse conduction and generation in the specific ways thought to produce arrhythmias. Reduction in the extracellular pH to 6.0 alone can cause production of slow responses in isolated, superfused canine Purkinje cells. The pH of ischemic ventricular tissue becomes reduced to this level, which raises the possibility that the fall in pH may contribute, in part, to the onset of slow responses and hence arrhythmias during myocardial ischemia. For this reason determination of the factors involved in production of pH-induced slow responses and their electrophysiological characteristics and behavior appear worthy of study. Specific experiments are outlined which appear capable of providing this information. The influence of antiarrhythmic drugs on pH-induced slow responses also will be determined. The results may find application in understanding the cellular electrophysiological mechanisms which underlie arrhythmogenesis as well as the mechanisms involved in antiarrhythmic action.